Poxviruses

Abstract

Poxviruses are brick‐shaped, enveloped viruses, each containing a linear, double‐stranded DNA (deoxyribonucleic acid) genome of 134–365 kilobases (kb). Several family members, including variola, monkeypox, cowpox, vaccinia, orf and molluscum contagiosum viruses, cause disease in humans. Smallpox, which was caused by variola virus, was once responsible for the deaths of millions each year. In 1796, Jenner showed that inoculation of material from a cowpox lesion could protect against smallpox: vaccination had been introduced into medicine. Moreover, through the use of cowpox and vaccinia virus vaccines, the dread disease of smallpox was eradicated from the natural environment. Although variola virus, the principal poxvirus pathogen, is no longer a public health hazard, the poxviruses have continued to be the focus of intense study because they provide unique systems for investigation of mechanisms important in molecular biology, viral pathogenicity and immunity. Attenuated poxviruses now provide some of the most promising contemporary platforms for broad‐spectrum, live‐virus vaccines.

Key Concepts

  • Variola virus, which causes smallpox, is one of the most virulent human pathogens.
  • Variola virus was the first virus to be eradicated from the natural environment.
  • Jenner showed that infection with cowpox could protect against infection with smallpox.
  • Cowpox virus was the original vaccine, hence the name vaccine, from the Latin word vacca for cow.
  • The worldwide eradication of the disease of smallpox was achieved by immunisation with vaccines containing live vaccinia viruses (viruses similar to, but more attenuated than, cowpox virus).
  • Except for variola virus and molluscum contagiosum virus (MCV), most of the poxvirus diseases of humans are zoonoses (diseases transmitted to humans from animals).
  • Among viruses, the poxviruses are unusually independent of host cell functions, employing mainly viral enzymes for viral gene transcription and viral DNA replication in the cytoplasm of infected cells.
  • Poxviruses do not establish latent infections.
  • Poxviruses possess many accessory genes that are not required for virus replication in vitro, but which are advantageous for virus replication in vivo.
  • Most of the accessory proteins encoded by poxviruses of vertebrates interfere with either innate or adaptive immune responses.

Keywords: cowpox; vaccinia; smallpox; vaccines; viral replication; virus‐host interactions

Figure 1. The poxvirus replication cycle. The replication cycle is depicted diagrammatically progressing from left to right. The upper panel shows morphological features of replication: (1) attachment, fusion and entry of the virus particles, where the EV outer membrane is disrupted or the matrix of the ATI is solubilised to release an MV capable of attachment to and fusion with the plasma membrane; (2) the uncoating of the MV to generate the cores; (3) the formation of viroplasm in the viral factories or viral B‐type inclusions; (4) the morphogenetic pathway leading from crescents to the formation of immature virus particles (IVs) that may contain electron‐dense condensed regions; (5) transition of the IVs into the mature virions (MVs); (6) the MVs subsequently enter one of the three pathways, namely retention in the cytoplasm, conversion into MVs embedded within the A‐type inclusions (ATIs) or conversion into the wrapped virions (WVs) possessing two additional membrane layers. The WVs are transported to the plasma membrane on microtubules. At the cell periphery, the outermost membrane of the WV fuses with the plasma membrane to produce an EV on the outer surface of the cell. This particle is then propelled from the cell on the tips of generated by the formation of actin tails in the cytoplasm under the cell‐associated EV. The EVs are projected from live cells. The residual MVs in the cytoplasm and the ATIs containing embedded MVs are released on death and disintegration of the infected cell. The lower panel depicts the onset of the various stages of the replication cycle relative to the time of infection.
Figure 2. Intermediates in poxvirus morphogenesis. A transmission electron micrograph of a thin section through the cytoplasm of a cell infected with showing several intermediate forms of the virus particle. Key: C, crescent; IV, immature virion; MV, mature virion and V, viroplasm (granular material containing viral DNA and proteins). The arrows indicate progressively more mature forms of virus particle. Note the characteristic dumbbell‐shaped core in the MV at the right‐hand edge of the figure. Electron micrograph courtesy of Dr Sara E Miller (Department of Pathology, Duke University Medical Centre).
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References

Afonso CL, Tulman ER, Delhon G, et al. (2006) Genome of crocodilepox virus. Journal of Virology 80: 4978–4991.

Alzhanova D, Edwards DM, Hammarlund E, et al. (2009) Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition. Cell Host & Microbe 6: 433–445.

Alzhanova D and Fruh K (2010) Modulation of the host immune response by cowpox virus. Microbes and Infection/Institut Pasteur 12: 900–909.

Babiuk S, Bowden TR, Boyle DB, Wallace DB, and Kitching, R.P. (2008). Capripoxviruses: an emerging worldwide threat to sheep, goats and cattle. Transboundary and Emerging Diseases 55, 263–272.

Baughman B, Zhang S, Jin L, et al. (2011) Diagnosis of Deerpox virus infection in a white‐tailed deer (Odocoileus virginianus) fawn. Journal of Veterinary Diagnostic Investigation Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 23: 965–970.

Bergman N, Moraes KC, Anderson JR, et al. (2007) Lsm proteins bind and stabilize RNAs containing 5' poly(A) tracts. Nature Structural & Molecular Biology 14: 824–831.

Berhanu A, King DS, Mosier S, et al. (2009) ST‐246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation. Antimicrobial Agents and Chemotherapy 53: 4999–5009.

Brady G and Bowie AG (2014) Innate immune activation of NFkappaB and its antagonism by poxviruses. Cytokine & Growth Factor Reviews 25: 611–620.

Byun M, Verweij MC, Pickup DJ, et al. (2009) Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells. Cell Host & Microbe 6: 422–432.

Chantrey J, Meyer H, Baxby D, et al. (1999) Cowpox: reservoir hosts and geographic range. Epidemiology and Infection 122: 455–460.

Chen X, Anstey AV and Bugert JJ (2013) Molluscum contagiosum virus infection. The Lancet Infectious Diseases 13: 877–888.

Cudmore S, Cossart P, Griffiths G and Way M (1995) Actin‐based motility of vaccinia virus. Nature 378: 636–638.

Damon I, Murphy PM and Moss B (1998) Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proceedings of the National Academy of Sciences of the United States of America 95: 6403–6407.

Damon IK (2013) Poxviruses. In: Knipe D and Howley PM, (eds). Fields Virology, pp. 2160–2184. Philadelphia: Lippincott Williams and Wilkins.

Doceul V, Hollinshead M, van der Linden L and Smith GL (2010) Repulsion of superinfecting virions: a mechanism for rapid virus spread. Science 327: 873–876.

Downie AW and Espana C (1972) Comparison of Tanapox virus and Yaba‐like viruses causing epidemic disease in monkeys. The Journal of Hygiene 70: 23–32.

Duraffour S, Meyer H, Andrei G and Snoeck R (2011) Camelpox virus. Antiviral Research 92: 167–186.

Esteban DJ and Buller RM (2005) Ectromelia virus: the causative agent of mousepox. The Journal of General Virology 86: 2645–2659.

Fenner F, Henderson DA, Arita I, Jezek Z and Ladnyi ID (1988a) The clinical features of smallpox. In: Smallpox and Its Eradication, pp. 1–68. Geneva: World Health Organization.

Fenner F, Henderson DA, Arita I, Jezek Z and Ladnyi ID (1988b) The intensified smallpox eradication programme, 1967–1980. In: Smallpox and Its Eradication, pp. 421–538. Geneva: World Health Organization.

Gubser C, Hue S, Kellam P and Smith GL (2004) Poxvirus genomes: a phylogenetic analysis. The Journal of General Virology 85: 105–117.

Hammarlund E, Dasgupta A, Pinilla C, et al. (2008) Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation. Proceedings of the National Academy of Sciences of the United States of America 105: 14567–14572.

Huchzermeyer FW, Huchzermeyer KD and Putterill JF (1991) Observations on a field outbreak of pox virus infection in young Nile crocodiles (Crocodylus niloticus). Journal of the South African Veterinary Association 62: 27–29.

Jezek Z, Arita I, Szczeniowski M, et al. (1985) Human tanapox in Zaire: clinical and epidemiological observations on cases confirmed by laboratory studies. Bulletin of the World Health Organization 63: 1027–1035.

Jin L, McKay A, Green R, Xu L and Bildfell R (2013) Serosurvey for antibody to deerpox virus in five cervid species in Oregon, USA. Journal of Wildlife Diseases 49: 186–189.

Johnston JB, Barrett JW, Nazarian SH, et al. (2005) A poxvirus‐encoded pyrin domain protein interacts with ASC‐1 to inhibit host inflammatory and apoptotic responses to infection. Immunity 23: 587–598.

Kerr PJ (2012) Myxomatosis in Australia and Europe: a model for emerging infectious diseases. Antiviral Research 93: 387–415.

Laliberte JP and Moss B (2014) A novel mode of poxvirus superinfection exclusion that prevents fusion of the lipid bilayers of viral and cellular membranes. Journal of Virology 88: 9751–9768.

Li P, Wang N, Zhou D, et al. (2005) Disruption of MHC class II‐restricted antigen presentation by vaccinia virus. Journal of Immunology 175: 6481–6488.

Medaglia ML, Pereira Ade C, Freitas TR and Damaso CR (2011) Swinepox virus outbreak, Brazil, 2011. Emerging Infectious Diseases 17: 1976–1978.

Milton DK (2012) What was the primary mode of smallpox transmission? Implications for biodefense. Frontiers in Cellular and Infection Microbiology 2: 150.

Moss B (2013a) Poxviridae. In: Knipe DM and Howley PM, (eds). Fields Virology, pp. 2129–2159. Philadelphia: Lippincott Williams and Wilkins.

Moss B (2013b) Poxvirus DNA replication. Cold Spring Harbor Perspectives in Biology 5: a010199.

Moss B, Carroll MW, Wyatt LS, et al. (1996) Host range restricted, non‐replicating vaccinia virus vectors as vaccine candidates. Advances in Experimental Medicine and Biology 397: 7–13.

Paoletti E (1996) Applications of pox virus vectors to vaccination: an update. Proceedings of the National Academy of Sciences of the United States of America 93: 11349–11353.

Parker S and Buller RM (2013) A review of experimental and natural infections of animals with monkeypox virus between 1958 and 2012. Future Virology 8: 129–157.

Perdiguero B and Esteban M (2009) The interferon system and vaccinia virus evasion mechanisms. Journal of Interferon & Cytokine Research 29: 581–598.

Ray CA, Black RA, Kronheim SR, et al. (1992) Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin‐1 beta converting enzyme. Cell 69: 597–604.

Roberts KL and Smith GL (2008) Vaccinia virus morphogenesis and dissemination. Trends in Microbiology 16: 472–479.

Shirokikh NE and Spirin AS (2008) Poly(A) leader of eukaryotic mRNA bypasses the dependence of translation on initiation factors. Proceedings of the National Academy of Sciences of the United States of America 105: 10738–10743.

Smee DF (2013) Orthopoxvirus inhibitors that are active in animal models: an update from 2008 to 2012. Future Virology 8: 891–901.

Smith GL, Benfield CT, Maluquer de Motes C, et al. (2013) Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity. The Journal of General Virology 94: 2367–2392.

Taylor JM and Barry M (2006) Near death experiences: poxvirus regulation of apoptotic death. Virology 344: 139–150.

Theze J, Takatsuka J, Li Z, et al. (2013) New insights into the evolution of Entomopoxvirinae from the complete genome sequences of four entomopoxviruses infecting Adoxophyes honmai, Choristoneura biennis, Choristoneura rosaceana, and Mythimna separata. Journal of Virology 87: 7992–8003.

Turner PC and Moyer RW (2008) The vaccinia virus fusion inhibitor proteins SPI‐3 (K2) and HA (A56) expressed by infected cells reduce the entry of superinfecting virus. Virology 380: 226–233.

Upton C, Slack S, Hunter AL, Ehlers A and Roper RL (2003) Poxvirus orthologous clusters: toward defining the minimum essential poxvirus genome. Journal of Virology 77: 7590–7600.

Wagenaar TR and Moss B (2009) Expression of the A56 and K2 proteins is sufficient to inhibit vaccinia virus entry and cell fusion. Journal of Virology 83: 1546–1554.

Weli SC and Tryland M (2011) Avipoxviruses: infection biology and their use as vaccine vectors. Virology Journal 8: 49.

Yang Z, Bruno DP, Martens CA, Porcella SF and Moss B (2011) Genome‐wide analysis of the 5' and 3' ends of vaccinia virus early mRNAs delineates regulatory sequences of annotated and anomalous transcripts. Journal of Virology 85: 5897–5909.

Yang Z, Martens CA, Bruno DP, Porcella SF and Moss B (2012) Pervasive initiation and 3'‐end formation of poxvirus postreplicative RNAs. The Journal of Biological Chemistry 287: 31050–31060.

Further Reading

Barry M, van Buuren N, Burles K, et al. (2010) Poxvirus exploitation of the ubiquitin‐proteasome system. Viruses 2: 2356–2380.

Cottingham MG and Carroll MW (2013) Recombinant MVA vaccines: dispelling the myths. Vaccine 31: 4247–4251.

Essbauer S, Pfeffer M and Meyer H (2010) Zoonotic poxviruses. Veterinary Microbiology 140: 229–236.

Gilbert SC (2013) Clinical development of modified vaccinia virus Ankara vaccines. Vaccine 31: 4241–4246.

Haller SL, Peng C, McFadden G and Rothenburg S (2014) Poxviruses and the evolution of host range and virulence. Infection, genetics and evolution. Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases 21: 15–40.

Kreijtz JH, Gilbert SC and Sutter G (2013) Poxvirus vectors. Vaccine 31: 4217–4219.

Mansur DS, Smith GL and Ferguson BJ (2014) Intracellular sensing of viral DNA by the innate immune system. Microbes and infection/Institut Pasteur 16: 1002–1012.

Schmidt FI, Bleck CK and Mercer J (2012) Poxvirus host cell entry. Current Opinion in Virology 2: 20–27.

Smith GL (2014) Rapid spreading and immune evasion by vaccinia virus. Advances in Experimental Medicine and Biology 808: 65–76.

Welch MD and Way M (2013) Arp2/3‐mediated actin‐based motility: a tail of pathogen abuse. Cell Host & Microbe 14: 242–255.

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Pickup, David J(Mar 2015) Poxviruses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001083.pub3]